The overall goal of this project is to develop and optimize a magnetic resonance imaging (MRI) technique for novel quantitative measurements of the macromolecular content and dynamics in tissues with special relevance to the characterization of brain myelin. The applicant has demonstrated in previous work that a novel MRI technique can be used to quantify (he ralio of the sizes of macromolecular and free water proton pools in biological systems, and provide a quantitative measure of the magnetization transfer (MT) rate constant between these different tissue subcomponents. The proposed studies will further develop and optimize this technique, will compare this technique to other MT techniques, and \vll use the optimum technique in combination with multi-component T2 measurements to investigate the changes in water cempartmeritation and exchange rates that occur in white matter and demyelinated lesions. The specific aims of the project are as follows: * to further develop selective inversion recovery (SIR) and to optimize both SIR and the pulsed saturation technique for speed, reliability, and accuracy for quantitatively measuring novel tissue properties. * to compare SIR to pulsed saturation and to validate both these methods against a known standard in a series of measurements on model biopolymers. * to evaluate optimized methods of quantitative MT imaging in biopolymers and in vivo in healthy rats. * to evaluate the sensitivity of quantitative MT imaging to changes in brain matter due to demyelination, inflamation, and axonal loss as revealed by histology, producing information that will further develop applications of MRI in multiple sclerosis.